European Patent Application No. 004913 as laid open describes inter alia a process for the production of 17-C-steroid-.alpha.-propionic acid compounds, particularly 3-oxo-pregna-4-ene-20-carboxylic acid (.DELTA.4-BNC) and/or 3-oxo-pregna-1,4-diene-20-carboxylic acid (.DELTA.1,4-BNC), by microbial side chain degradation on 17-C-side chain steroid substrates. By using defect mutant microorganisms grown and selected in a certain manner, which give steroid compounds containing the 17-C-.alpha.-propionic acid residue even in the absence of inhibitors which inhibit degradation of the steroid ring and/or growth inhibitors, it is possible to obtain .DELTA.4-BNC and, in particular, .DELTA.1,4-BNC in commercial quantitites. Another of this process is described in laid open European Patent Application No. 0015308.
German Offenlegungsschrift No. 28 39 033 also laid open, describes structurally analogous steroid-20-carboxylic acids containing an additional double bond in the 9(11)-position and a process for their production. In particular, one possibility of producing .DELTA.1,4,9(11)-BNC is described therein. .DELTA.4,9(11)-BNC is described in U.S. Pat. No. 4,062,880. All these compounds, particularly .DELTA.4-BNC, .DELTA.1,4-BNC and .DELTA.1,4,9(11)-BNC, contain a functional group in only the 3-position of the ring system. However, all pharmacologically active corticosteroids contain additional oxygen functions. The 11,17 and 21 positions inter alia are particularly important in this respect. Normally, some of these oxygen functions are chemically introduced, including in particular the 17 and 21 positions.
By contrast, oxidation of the 11-position is steroid compounds is preferably carried out microbially. Several such microbial steroid oxidation processes are described in the literature. In this connection, reference is made to the following publications and to the original Articles quoted therein:
F. Drawert "Biosynthese von Hydroxy-Verbindungen (Biosynthesis of Hydroxy-Compounds)"; Houben-Weyl "Methoden der organischen Chemie" (1978) 6/ld, pages 378 to 388; T. H. Stoudt, Adv. Appl. Microbiol. 2 (1960), pages 190 to 195 and W. Charney and H. L. Herzog "Microbial Transformations of Steroids", Academic Press (1967) New York, N.Y. page 29.
The microbial 11-hydroxylation of a variety of steroid compounds and the synthesis products obtained are described in these publications with numerous reference to certain microorganism strains, particularly from the class of fungi.
The 11.beta.-hydroxyl or 11-oxo configuration is generally required for strong, pharmacological activity. Steroids hydroxylated in the 11.beta.-position are obtained either by using microorganism strains which introduce a hydroxyl group of the type in question stereoselectively or by using other microorganisms which hydroxylate in the 11.beta.-position either predominantly or completely stereoselectively. In this case, the 11.beta.-hydroxylated steroids are obtained by chemical oxidation to the 11-ketone in a first step, followed by reduction with a suitable reducing agent. The 11.beta.-hydroxy compound can be formed stereoselectively. So far as the relevant literature on this subsequent chemical transformation is concerned, reference is made for example to I. F. Fieser, M. Fieser Steroide "(Steroids)", Verlag Chemie (Weinheim 1961), pages 737 et seq and to the original literature reference cited therein, J. Am. Chem. Soc. 77, 4436 (1955).
Pharmacologically important steroid compounds and intermediate products for their production, for example progesterone, compounds of the cortisone series and compounds of the prednisone series, no longer contain the C-22-carboxyl group which is present as a substituent in the 20-position in BNC-compounds.
Earlier and co-pending commonly assigned Patent Applications describe the transformation of the 20-carboxyl group in the BNC-compounds mentioned into the corresponding 20-acid halide group. In particular, the corresponding acid chlorides and their production are described. Thus, commonly-assigned earlier European Patent Application No. 81,100,145.2 describes inter alia pregna-1,4-diene-3-one-20-carbonyl chloride (.DELTA.1,4-BNC-chloride) and a process for its production. This acid chloride, which is a functional derivative of the associated .DELTA.1,4-BNC, is suitable for use as a starting material for subsequent reactions for the further structural transformation of the side chain substituent in the 17-position of the steroid ring skeleton. The production of other steroid-20-carboxylic acid halides of the type mentioned is described in commonly-assignly copending Patent Application Ser. No. 262,971, filed May 12, 1981, entitled "New Steroid-20-carboxylic acid compounds and a process for their production", now abandoned in favor of its continuation-in-part application Ser. No. 423,276, filed Sept. 24, 1982, Priority Austria A 2629/80 filed May 16, 1980 and 262,965, filed May 12, 1981, entitled "New pregnane-20-carboxylic acid derivatives and a process for their production", now abandoned in favor of its continuation-in-part application Ser. No. 407,790, filed Aug. 13, 1982, Priority Austria No. A 2535/80 filed May 12, 1980.